Specificity of coxsackievirus B3 interaction with human, but not murine, decay-accelerating factor: replacement of a single residue within short consensus repeat 2 prevents virus attachment

J Virol. 2015 Jan 15;89(2):1324-8. doi: 10.1128/JVI.02798-14. Epub 2014 Nov 12.


Many coxsackievirus B (CVB) isolates bind to human decay-accelerating factor (DAF) as well as to the coxsackievirus and adenovirus receptor (CAR). However, the virus does not interact with murine DAF. To understand why CVB3 binds specifically to human DAF, we constructed a series of chimeric molecules in which specific regions of the human DAF molecule were replaced by the corresponding murine sequences. We found that replacement of human short consensus repeat 2 (SCR2) with murine SCR2 ablated virus binding to human DAF, as did deletion of human SCR2. Although replacement of human SCR4 had a partial inhibitory effect, deletion of SCR4 had no effect. Within human SCR2, replacement of serine 104 (S104) with the proline residue found in murine DAF eliminated virus binding. On the basis of the structure of the CVB3-DAF complex determined by cryo-electron microscopy, DAF S104 is in close contact with a viral capsid residue, a threonine at VP1 position 271. Replacement of this capsid residue with larger amino acids specifically eliminated virus attachment to human DAF but had no effect on attachment to CAR or replication in HeLa cells. Taken together, these results support the current model of virus-DAF interaction and point to a specific role for VP1 T271 and DAF S104 at the virus-DAF interface.

Importance: The results of the present study point to a specific role for VP1 T271 and DAF S104 at the interface between CVB3 and DAF, and they demonstrate how subtle structural changes can dramatically influence virus-receptor interactions. In addition, the results support a recent pseudoatomic model of the CVB3-DAF interaction obtained by cryo-electron microscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD55 Antigens / genetics
  • CD55 Antigens / metabolism*
  • Capsid Proteins / metabolism*
  • Cell Line
  • DNA Mutational Analysis
  • Enterovirus B, Human / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Virus Attachment*


  • CD55 Antigens
  • Capsid Proteins
  • Receptors, Virus